Development of a physiologically based pharmacokinetic model for estradiol in rats and humans: a biologically motivated quantitative framework for evaluating responses to estradiol and other endocrine-active compounds.
Development of a physiologically based pharmacokinetic model for estradiol in rats and humans: a biologically motivated quantitative framework for evaluating responses to estradiol and other endocrine-active compounds.
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开发大鼠和人类雌二醇的生理学药代动力学模型：用于评估对雌二醇和其他内分泌活性化合物的反应的生物学驱动的定量框架。
DOI：
10.1093/toxsci/69.1.60
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
J. Teeguarden
中科院分区：
文献类型：
--
作者：
D. Plowchalk;J. Teeguarden
建立了雌二醇（E2）在大鼠和人（雄性和雌性）体内的生理药代动力学（PBPK）模型，为评价生理参数对E2血液和组织浓度时间过程的重要性以及预测大鼠和人的血液和组织浓度提供了定量工具。建立了一个肝提取模型，以评估血浆蛋白结合对肝提取E2的意义，并将该方法集成到E2模型中。有足够的数据可用于参数化和验证口服和静脉途径。E2血液和组织浓度的E2模型模拟与实验值比较良好。雌激素受体含量强烈影响E2的分布和消除动力学以及组织浓度。静脉推注给药后观察到的延长的终末消除相反映了受体结合的E2从组织中的缓慢释放。E2摄取行为在卵巢切除，但不是完整的大鼠子宫，最好的描述为扩散限制。模拟肝脏提取模型预测广泛的结合E2白蛋白（大鼠）和SHBG（性激素结合球蛋白人类），虽然肝脏提取似乎并不局限于未结合的部分，这意味着总血浆E2浓度是重要的，当考虑肝脏摄取。E2处置的重要决定因素是组织ER含量和结合亲和力、非受体结合蛋白、血管通透性、分配系数、肝血流量和肝外代谢。作为研究计划的一个组成部分，为E2开发的定量框架可以扩展到其他内分泌活性化合物（EAC），并用于评估EAC的生物活性。
A physiologically based pharmacokinetic (PBPK) model for estradiol (E2) in rats and humans (male and female) was developed to provide a quantitative tool for evaluating the importance of physiological parameters on E2 blood and tissue concentration time-course and for predicting blood and tissue concentrations in rats and humans. A hepatic extraction model was developed to evaluate the significance of plasma protein binding on the hepatic extraction of E2 and the approach was integrated into the E2 model. Sufficient data was available to parameterize and validate oral and iv routes. The E2 model simulations of E2 blood and tissue concentrations compared well to experimental values. Estrogen receptor content strongly impacts distribution and elimination kinetics of E2 as well as tissue concentrations. The prolonged terminal elimination phase seen after iv bolus administration reflects the slow release of receptor bound E2 from tissues. E2 uptake behavior in the ovariectomized, but not intact rat uterus, was best described as diffusion-limited. Simulations with the hepatic extraction model predicted extensive binding of E2 to albumin (rat) and SHBG (sex-hormone binding globulin humans), although hepatic extraction does not appear to be restricted to the unbound fraction, implying that the total plasma E2 concentration is important when considering hepatic uptake. Important determinants of E2 disposition are tissue ER content and binding affinity, nonreceptor binding proteins, vascular permeability, partition coefficients, hepatic blood flow, and extrahepatic metabolism. As an integral part of a research program, the quantitative framework developed for E2 can be extended to other endocrine-active compounds (EACs) and used to evaluate the biological activity of EACs.
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大鼠子宫中血管内皮生长因子/血管通透性因子的表达：雌激素的快速刺激与雌激素诱导的子宫毛细血管通透性和生长的增加相关。
影响因子：
4.8
作者：
Cullinan-Bove,K;Koos,RD
通讯作者：
Koos,RD
子宫和肝脏血管床对雌激素和雌激素结合物的不同渗透性。
DOI：
10.1210/jcem-59-6-1128
发表时间：
1984
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
Verheugen,C;Pardridge,WM;Judd,HL;Chaudhuri,G
通讯作者：
Chaudhuri,G
血浆蛋白结合配体血脑屏障转运的示踪动力学模型。
DOI：
10.1172/jci111490
发表时间：
1984
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Pardridge,WM;Landaw,EM
通讯作者：
Landaw,EM
电子屏幕测定作为识别雌激素的工具：雌激素环境污染物的更新。
影响因子：
10.4
作者：
通讯作者：
--
睾酮在大脑中的转运：血浆蛋白结合激素的主要作用。
DOI：
10.1152/ajpendo.1985.249.5.e534
发表时间：
1985
期刊：
The American journal of physiology
影响因子：
--
作者：
Pardridge,WM;Landaw,EM
通讯作者：
Landaw,EM